Incidence and sex-related risk factors of linezolid-associated adverse drug reactions identified through electronic health records.

Linezolid is an oxazolidinone antibiotic widely used to treat gram-positive infections and is associated with frequent adverse drug reactions (ADRs). Nevertheless, comprehensive evaluations of the incidence and risk factors of linezolid-related ADRs remain limited, with substantial variability across studies. This study aimed to evaluate the incidence of linezolid-associated ADRs and identify potential risk factors. A retrospective analysis was conducted using the Clinical Data Warehouse of Seoul National University Bundang Hospital (2003-2025). Among patients receiving at least one dose of linezolid, thrombocytopenia, neutropenia, anemia, leukopenia, and lactic acidosis were identified as ADRs. Kaplan-Meier analysis assessed cumulative incidence, and univariable and multivariable logistic regression were performed to identify risk factors. Among 1,198 patients, the cumulative incidences of thrombocytopenia, anemia, leukopenia, neutropenia, and lactic acidosis within three months after linezolid treatment initiation were 44.7%, 57.3%, 45.8%, 29.9%, and 27.5%, respectively. Concomitant use of trimethoprim-sulfamethoxazole was associated with anemia, while female sex and receipt of fresh frozen plasma transfusion were associated with lactic acidosis. Red blood cell transfusion was associated with an increased incidence of thrombocytopenia. This study demonstrated a higher incidence of linezolid-associated ADRs than previously reported in registration clinical trials. While several concomitant medications and clinical factors were identified as potential risk factors, associations involving transfusion-related variables should be interpreted cautiously, as they likely reflect underlying clinical vulnerability rather than a direct causal effect. These findings emphasize the importance of ADR monitoring during linezolid therapy and further research on the underlying mechanisms of linezolid-associated toxicity.